DESCRIPTION (Applicant's Abstract): Massage therapy (in the form of Manual Lymph Drainage (MLD) or Manual Lymphedema Treatment (MLT) is an integral component of the international consensus-recommended optimal treatment for lymphedema(LE) of the arms and legs, which according to the World Health Organization affects hundreds of millions worldwide. Indeed, for more than a century, close links between various forms of massage and salutary effects on lymph circulation have been postulated. Nonetheless, experimental work and clinical trials have not yielded clear evidence that MLD alone (without accompanying mechanical compression) is efficacious in preventing or ameliorating LE in its early stages of high-protein fluid accumulation or particularly when lymphostasis has been long-standing with associated soft tissue hardening (elephantiasis). Furthermore, the precise protocol of MLO as part of CPT or for testing as an independent modality as well as the optimal quantitative measures to be followed have not been objectively evaluated. This exploratory proposal will utilize our newly refined standardized LE animal model, closely resembling the clinical condition following radical groin dissection/radiation for cancer. Unilateral hindlimb LE is produced in Wistar-fuzzy rats by unilateral surgery + radiation (consisting of sequential operative inguinal lymphatic ablation and lymphadenectomy followed by localized groin irradiation). Control contralateral limbs and control unmanipulated and sham-manipulated rats will serve for comparisons. Aided by refined lymphatic/soft tissue imaging/analytic modalities, we will examine and compare quantifiable evidence of the efficacy of varying "doses" and regimens of MLD alone and in combination with mechanical compression including "mechanical massage" by sequential multi-chamber pneumatic compression pumping in enhancing lymphatic absorptive capacity to meet the lymphatic obligatory load, reducing LE volume or preventing LE, and remolding the LE limb in early largely fluid LE and subsequently, in chronic LE with fibrosis and bulky fat deposits. We will also assess additive and synergistic interactions among the various manipulative approaches miniaturized and standardized for the rodent model. This exploratory study will lay the groundwork and evidence-based rationale for the subsequent design and implementation of randomized cross-over clinical trial of MLD alone and in combination with different forms of mechanical compression in prevention and treatment of various forms and stages of upper and lower limb LE in children and adults. It will also provide a useful practical standardized LE animal model for detailed delineation of physiologic mechanisms/effects in the lymphatic system, and (lymph)edema postulated for a wide array of inadequately tested alternative/complementary approaches (e.g. herbal remedies, manipulative methods, diathermy) in current popular use around the world as "lymphotonics" and/or for LE treatment.